1998 Fiscal Year Annual Research Report

癌抑制遺伝子の作用機構

Research Project

Project/Area Number	06283215
Research Institution	The University of Tokyo
Principal Investigator	秋山徹東京大学, 分子細胞生物学研究所, 教授 (70150745)
Co-Investigator(Kenkyū-buntansha)	石館宇夫東京大学, 分子細胞生物学研究所, 助手 (70301116)
Keywords	β-catenin / Axin / D-Axin / Slimb / βTrCP / ICAT / APCL / SPAL
Research Abstract	1. β-catenin結合蛋白質を3種類見い出し、その内の一つがAxinで、β-catenin,GSK-3β,APCと結合してβ-cateninの分解を誘導する活性をもつことを見い出した。 2. APCがb-cateninの分解を誘導するためにはAxinと結合することが必要であることを明らかにした。 3. Drosophilaを用いた遺伝学的解析により、Axinファミリーの蛋白質がWnt/Winglessシグナル伝達経路の負の制御因子であることを証明した。 4. Drosophilaで見い出されたSlimbのヒトホモログβTrCPがβ-caateninのユビキチン化に関与していることを明らかにした。 5. ICATと名付けた新規β-catenin結合蛋白質は、β-catenin-TCF複合体に結合してTCFのDNAへの結合を阻害することによりβ-catenin-TCF複合体による標的遺伝子の転写活性化を抑制することを見い出した。 6. ヒトおよびDrosphilaにAPCと類似した第2のAPC遺伝子が存在することを見い出した。 7. APCと結合するhDLGにさらに結合する蛋白質を見い出し、Rap1特異的なGAP活性をもつことを見い出した。 8. β-catenin-Tcf4複合体の標的遺伝子の単離を試み、候補遺伝子を単離した。

Research Products
(13 results)

All Other

All Publications (13 results)

[Publications] T.Nakamura et al.: "Axin,an inhibitor of the Wnt signaling pathway,interacts with β-catenin,GSK-3β and APC and reduces the β-catenin level." Genes Cells. 3. 395-403 (1998)
[Publications] T.Senda et al.: "Expression and localization of the APC tumor suppressor protein in the nervous system." Neuroscience. 83. 857-866 (1998)
[Publications] K.Inoue et al.: "Wilms' tumor gene (WT1) competes with differentiation-inducing signal in hematopoietic progenitor cells." Blood. 91. 2969-2976 (1998)
[Publications] H.Nakagawa et al.: "Identification of a brain-specific APC homologue,APCL,and its interaction with β-catenin." Cancer Res.58. 5176-5181 (1998)
[Publications] Y.Dabashi et al.: "CDK4,a possible critical regulator of apoptosis in rat pheochromocytoma PC12 cells." Biochem.Biophys.Res.Commun.253. 609-613 (1998)
[Publications] T.Yamagami et al.: "Suppression of Wilms' tumor gene (WT1) expression induces G2/M arrest in leukemic cells." Leuk.Res.22. 383-384 (1998)
[Publications] K.Mori et al.: "Identification of brain-specific splicing variants of the hDLG1 gene and altered splicing in neuroblastoma cell lines." J.Hum.Genet.43. 123-127 (1998)
[Publications] T.Yamochi et al.: "Adenovirus-mediated high expression of BCL-6 in CV-1 cells induces apoptotic cell death accompanied by downregulation of BCL-2 and BCL-XL." Oncogene. 18. 487-494 (1999)
[Publications] T.Tezuka et al.: "PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A." Proc.Natl.Acad.Sci.USA96. 435-440 (1999)
[Publications] F.Hamada et al.: "Negative regulation of Wingless signaling by D-Axin,a Drosophila homologue of Axin." Science. 283. 1739-1742
[Publications] T.Senda et al.: "Association of the MCC (Mutated in colorectal cancer) gene product to the plasma membrane and membrane organelles." Medical Electron Microscopy. (in press).
[Publications] M.Takemura et al.: "Nucleolar protein B23.1 binds to retinoblastoma protein and synergistically stimulates DNA polymerase alpha activity." J.Biochem.(in press).
[Publications] R.B.Chandra et al.: "Localization of the GAP family SPAL in the Rat Esophagus and Heart." Medical Electronmicroscopy. (in press).

1998 Fiscal Year Annual Research Report

癌抑制遺伝子の作用機構

Principal Investigator

秋山 徹 東京大学, 分子細胞生物学研究所, 教授 (70150745)

Research Products

[Publications] T.Nakamura et al.: "Axin,an inhibitor of the Wnt signaling pathway,interacts with β-catenin,GSK-3β and APC and reduces the β-catenin level." Genes Cells. 3. 395-403 (1998)

[Publications] T.Senda et al.: "Expression and localization of the APC tumor suppressor protein in the nervous system." Neuroscience. 83. 857-866 (1998)

[Publications] K.Inoue et al.: "Wilms' tumor gene (WT1) competes with differentiation-inducing signal in hematopoietic progenitor cells." Blood. 91. 2969-2976 (1998)

[Publications] H.Nakagawa et al.: "Identification of a brain-specific APC homologue,APCL,and its interaction with β-catenin." Cancer Res.58. 5176-5181 (1998)

[Publications] Y.Dabashi et al.: "CDK4,a possible critical regulator of apoptosis in rat pheochromocytoma PC12 cells." Biochem.Biophys.Res.Commun.253. 609-613 (1998)

[Publications] T.Yamagami et al.: "Suppression of Wilms' tumor gene (WT1) expression induces G2/M arrest in leukemic cells." Leuk.Res.22. 383-384 (1998)

[Publications] K.Mori et al.: "Identification of brain-specific splicing variants of the hDLG1 gene and altered splicing in neuroblastoma cell lines." J.Hum.Genet.43. 123-127 (1998)

[Publications] T.Yamochi et al.: "Adenovirus-mediated high expression of BCL-6 in CV-1 cells induces apoptotic cell death accompanied by downregulation of BCL-2 and BCL-XL." Oncogene. 18. 487-494 (1999)

[Publications] T.Tezuka et al.: "PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A." Proc.Natl.Acad.Sci.USA96. 435-440 (1999)

[Publications] F.Hamada et al.: "Negative regulation of Wingless signaling by D-Axin,a Drosophila homologue of Axin." Science. 283. 1739-1742

[Publications] T.Senda et al.: "Association of the MCC (Mutated in colorectal cancer) gene product to the plasma membrane and membrane organelles." Medical Electron Microscopy. (in press).

[Publications] M.Takemura et al.: "Nucleolar protein B23.1 binds to retinoblastoma protein and synergistically stimulates DNA polymerase alpha activity." J.Biochem.(in press).

[Publications] R.B.Chandra et al.: "Localization of the GAP family SPAL in the Rat Esophagus and Heart." Medical Electronmicroscopy. (in press).

秋山徹東京大学, 分子細胞生物学研究所, 教授 (70150745)